Modafinil, d‐amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature

Abstract

Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty-one military subjects received either 300 mg of modafinil, 20 mg of d-amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side-effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations.

The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia

“…Modafinil improves vigilance, logical reasoning, short-term memory and tracking tasks in sleep-deprived healthy volunteers and patients with narcolepsy [18,19,20]. Its mechanism of action is not completely understood but is believed to work through its action on brain GABA levels.…”

“…Modafinil, used in the treatment of narcolepsy, lowers brain GABA concentration. It is a wakefulness-promoting agent that improves vigilance and cognitive performance during sleep deprivation in patients with narcolepsy and in healthy volunteers [18,19,20]. We examined whether this agent, with acute administration, enhances counter-regulatory responses to hypoglycaemia in human subjects.…”

The Efficacy of Modafinil for Sustaining Alertness and Simulator Flight Performance in F-117 Pilots During 37 Hours of Continuous Wakefulness

“…In addition, a single 20 mg dose has been found to temporarily prevent performance decrements in subjects kept awake for approximately 34 hours, and to restore the performance of volunteers deprived of sleep for 48 hours (Pigeau et al, 1995). Multiple 10-mg doses of dextroamphetamine, administered prophylactically, are known to sustain the performance of heUcopter pilots throughout 40 hours of continuous wakefulness (Caldwell et al, 1995;Caldwell, Caldwell, and Crowley, 1996;Caldwell and Caldwell, 1997), and even throughout 64 hours without sleep .…”

“…For instance, and found that modafinil reduced the frequency of involuntary sleep lapses and maintained cognitive performance during 60 hours of continuous wakefulness. Pigeau et al (1995) reported that modafinil (300 mg) was as effecfive as dextroamphetamine (20 mg) for maintaining mood, alertness, and performance throughout 64 hours of sleep deprivation. Eddy et al (2001) reported that modafinil eliminated fatigue-related performance decrements on a vigilance task in people kept awake for 22 hours, and Wesensten et al (2002) indicated that modafinil (200 mg and 400 mg) effectively counteracted cognitive performance decrements resulting from 41.5 hours of continuous wakefulness.…”

Where is the classic interference theory for sleep and memory?

“…Nicotine enhances memory and attention but inhibits sleep-promotion while facilitating other wake-promoting systems in normal and AD individuals (Saint-Mleux et al 2004;Wilson et al 1995). Modafinil induces prolonged wakefulness in normal individuals, enabling 64 hours of sustained mental effort (Pigeau et al 1995) and enhances cognition (Turner et al 2003).…”